A Phase I Trial of a Methionine Restricted Diet with Concurrent Radiation Therapy.

Methionine is an essential amino acid critical for cell growth and survival. Preclinical evidence suggests a methionine restricted diet (MRD) sensitizes cancer to radiation therapy (RT), without significant adverse effects. However, this has never been evaluated in humans. The purpose of this pilot study was to evaluate the safety and feasibility of concurrent MRD with standard-of-care definitive RT in adults with any non-skin cancer malignancy. The MRD extended from 2 wk before RT initiation, through 2 wk beyond RT completion. The primary endpoint of safety was assessed as rate of grade 3 or higher acute and late toxicities. Feasibility was assessed with quantitative plasma amino acid panel every 2 wk during the MRD (target plasma methionine 13 µM). Nine patients were accrued over a two-year period, with five able to complete the treatment course. The trial was closed due to slow accrual and subjects' difficulty maintaining the diet. No grade 3 or higher adverse events were observed. Subjects' average methionine level was 18.8 µM during treatment, with average nadir 16.8 µM. These findings suggest the safety of concurrent MRD with RT, with toxicities comparable to those expected with RT alone. However, the diet was challenging, and unacceptable to most patients.

Intraoperative Radiotherapy in Brain Malignancies: Indications and Outcomes in Primary and Metastatic Brain Tumors.

Despite the continued controversy over defining an optimal delivery mechanism, the critical role of adjuvant radiation in the management of surgically resected primary and metastatic brain tumors remains one of the universally accepted standards in neuro-oncology. Local disease control still ranks as a significant predictor of survival in both high-grade glioma and treated intracranial metastases with radiation treatment being essential in maximizing tumor control. As with the emergence and eventual acceptance of cranial stereotactic radiosurgery (SRS) following an era dominated by traditional radiotherapy, evidence to support the use of intraoperative radiotherapy (IORT) in brain tumors requiring surgical intervention continues to accumulate. While the clinical trial strategies in treating glioblastoma with IORT involve delivery of a boost of cavitary radiation prior to the planned standard external beam radiation, the use of IORT in metastatic disease offers the potential for dose escalation to the level needed for definitive adjuvant radiation, eliminating the need for additional episodes of care while providing local control equal or superior to that achieved with SRS in a single fraction. In this review, we explore the contemporary clinical data on IORT in the treatment of brain tumors along with a discussion of the unique dosimetric and radiobiological factors inherent in IORT that could account for favorable outcome data beyond those seen in other techniques.

Radiographic and Tumor Biomarker Response to Radiotherapy for Recurrent Granulosa Cell Tumor of the Ovary.

Granulosa cell tumors (GCTs) of the ovary are rare, comprising less than 5% of all malignant ovarian neoplasms. While generally considered indolent, GCTs have a tendency for metastasis and delayed relapse, with recurrence developing in 20%-50%. Recurrent or metastatic disease is associated with aggressive behavior and a poor prognosis, as nearly 70% of patients developing recurrence will eventually succumb to their disease. The optimal management of relapsed disease is controversial. Initial salvage therapy typically involves surgical debulking followed by cisplatin-based chemotherapy. Unfortunately, tumor responses are durable for less than half of patients treated with this regimen. Radiation therapy is an attractive option for providing rapid palliation and improving local control without the morbidity of additional surgery or chemotherapy. Here we describe a case of multiply recurrent, rapidly growing intraperitoneal GCT refractory to repeated surgical debulking and several lines of systemic therapy. The patient was treated with two courses of palliative radiotherapy and achieved rapid symptomatic relief, achieving over a 90% reduction in tumor volume. Serum concentration of inhibin B, often inappropriately elevated in patients with GCT, decreased by 98% following irradiation with no interim systemic therapy. At one-year follow-up, the patient has no evidence of radiographic or biochemical recurrence.

A Prospective Trial Evaluating the Safety and Systemic Response From the Concurrent Use of Radiation Therapy with Checkpoint Inhibitor Immunotherapy in Metastatic Non-Small Cell Lung Cancer.

INTRODUCTION/BACKGROUND: This study assessed the safety and systemic (abscopal) response from the addition of local stereotactic body radiation therapy (SBRT) to checkpoint inhibitor (CPI) immunotherapy in patients with metastatic non-small cell lung cancer. PATIENTS/METHODS: Thirty-five patients with at least 2 sites of measurable disease on PET/CT received standard-of-care CPI immunotherapy alone (n = 19), or in combination with 4 cycles doublet carboplatin/pemetrexed chemotherapy (n = 16), and 3 to 5 fractions SBRT to a single extracranial target lesion between cycles 1 to 2 of the systemic therapy. Adverse events were assessed using CTCAE version 5.0. Best systemic objective response rate (ORR) was assessed using iRECIST criteria, excluding any irradiated lesion(s). Additional SBRT to a different target lesion was offered to patients who continued on immunotherapy with unconfirmed progressive disease or mixed response. RESULTS: Fifteen patients (44%) experienced 22 grade 1 to 2 toxicities potentially attributable to radiation, most commonly pneumonitis (n = 9) and fatigue (n = 6), and no grade 3 to 5 radiation-induced toxicities. Patients undergoing combined CPI-chemotherapy received a lower median biologically effective dose of SBRT than those undergoing CPI monotherapy (43.2 vs. 60Gy), but had a higher rate of radiation-induced toxicity (56% vs. 32%, P < .01). The best systemic ORR was 53%, with 20.5% stable disease and 26.5% progressive disease. Fifteen patients underwent a subsequent course of SBRT based on their response, among which 3 (20%) had progression-free intervals of 12, 16, and 10 months thereafter. CONCLUSIONS: Addition of SBRT to CPI immunotherapy (with/without chemotherapy) is safe. The favorable systemic response observed warrants further assessment with a randomized trial.

Intraoperative Radiation Therapy Versus Whole Breast Radiation for Early-Stage Breast Cancer Treatment in Rural Appalachia.

BACKGROUND: Intraoperative radiation therapy (IORT) is an alternate accelerated form of radiation following breast-conserving surgery (BCS). Lack of data regarding long-term outcomes has limited adoption. We report our experience with IORT in patients undergoing BCS versus whole breast radiation therapy (WBRT). METHODS: Retrospective review of patients undergoing BCS with IORT versus WBRT (2012-2017). Inclusion: low grade, T1-2N0M0, estrogen receptor/progesterone receptor positive, and Her2-negative infiltrating ductal carcinomas. IORT was delivered as a single fraction of radiation (20 Gy) intraoperatively. Outcomes were compared using Fisher's test for discrete variables or Wilcoxon signed-rank test for continuous variables. Kaplan-Meier method was used to estimate disease-free survival (DFS). RESULTS: Fifty-one patients (44%) received IORT, and 66 (56%) received WBRT. There was no difference in age, tumor size, receptor status, or in-breast recurrence (1.9% vs 0%, all P > .05). Length of follow-up was longer in the WBRT group due to time to inception of IORT (mean ± SD: 44 ± 8.1 vs 73 ± 13 months, P < .001). There was no difference in DFS between the 2 groups (HR 2.5; P = .44). IORT patients experienced delay to BCS (mean ± SD: 38 ± 12.7 vs 27 ± 12.2 days, P < .001) likely due to coordination of care. Analysis demonstrated IORT patients would have traveled a mean distance of 20 miles to the closest WBRT center (range 1-70, miles) for a mean travel time of 31 minutes (range 4-90, minutes) per WBRT treatment. DISCUSSION: IORT produces noninferior oncologic outcomes and decreased skin toxicity compared with WBRT. It can be convenient for patients in rural regions with limited health care access.

The Lack of Consensus of International Contouring Guidelines for the Dorsal Border of the Chest Wall Clinical Target Volume: What is the Impact on Organs at Risk and Relationships to Patterns of Recurrence in the Modern Era?

PURPOSE: Variation exists in cooperative group recommendations for the dorsal border for the chest wall clinical target volume (CTV). We aimed to quantify the impact of this variation on doses to critical organs and examine patterns of chest wall recurrence relative to the pectoralis muscle. METHODS AND MATERIALS: We retrospectively assessed patterns of chest wall recurrence quantified to the recommended CTV borders for women treated between 2005 and 2017. We compared treatment plans for 5 women who were treated with left postmastectomy radiation therapy, with the chest wall contoured using varying dorsal borders for CTV: (1) Anterior pleural surface (Radiation Therapy Oncology Group), (2) anterior surface of pectoralis major (European Society for Radiotherapy and Oncology), and (3) anterior rib surface (institutional practice). Treatment plans were generated for 50 Gy in 25 fractions. Doses to organs-at-risk were compared using paired-sample t tests. RESULTS: Institutional patterns of chest wall recurrence were 64.7% skin and subcutaneous tissue, 23.5% both anterior to and between the pectoralis muscles, and 11.8% isolated to the tissue between the pectoralis major and minor. No chest wall recurrences were noted deep to pectoralis minor. When comparing the plans generated per the Radiation Therapy Oncology Group versus European Society for Radiotherapy and Oncology contouring guidelines, the mean lung V20Gy, heart mean dose, and left anterior descending artery mean dose were 33.5% versus 29.4% (P < .01), 5.2 Gy versus 3.2Gy (P = .02), and 27.3Gy versus 17.8Gy (P = .04), respectively. CONCLUSIONS: The recommended variations in the dorsal chest wall CTV border have significant impact on doses to the heart and lungs. Although our study was limited by small numbers, our institutional patterns of recurrence would support a more anterior dorsal border for the chest wall CTV consistent with older literature.

Prognostic factors in breast cancer patients evaluated by positron-emission tomography/computed tomography before neoadjuvant chemotherapy.

Neoadjuvant chemotherapy (NAC) is a significant modality in breast cancer therapy. We sought to characterize prognostic factors in patients scheduled for NAC who had a pretreatment positron-emission tomography paired with diagnostic quality contrast-enhanced computed tomography (CT) (positron-emission tomography/CT [PET/CT]). A total of 118 breast cancer patients were analyzed through chart review who underwent pretreatment PET/CT imaging and received NAC from 2008 to 2014. We collected information on molecular markers, PET/CT, pathologic complete response (pCR), survival, and disease status. Pretreatment standard uptake value (SUV) max of the primary breast tumor showed no relationship to pCR; however, there was a statistically significant relationship with relapse-free survival (RFS) using univariate cox regression (P = 0.03, odds ratio (OR) = 1.06 [1.01-1.12]) with comparable findings observed with overall survival (OS). Multivariate analysis revealed SUV max to be significantly correlated with shortened OS (P = 0.022, OR = 1.08 [1.01-1.16]), with a similar trend reported for RFS. By pathological subtype, this correlation was the strongest within hormone receptor (HR+)/human epidermal growth factor receptor 2 (HER2-) tumors. In addition, Kaplan-Meier estimates demonstrated a significant difference between the RFS of triple-negative tumors and HER2 positive tumors (P = 0.001). Interestingly, within this cohort, multivariate Cox regression analysis showed HER2 positivity to be associated with favorable outcome (P = 0.04, HR = 0.22 [0.05-0.94]). These findings demonstrate a significant association between SUV max of HR+/HER2-- tumors and relapse-free and OS. Furthermore, highlighted here is the favorable survival in the once classically aggressive HER2+ breast cancer subgroup.

Feasibility of dose escalation using intraoperative radiotherapy following resection of large brain metastases compared to post-operative stereotactic radiosurgery.

BACKGROUND AND PURPOSE: Post-operative SRS (stereotactic radiosurgery) for large brain metastases is challenged by risks of radiation necrosis that limit SRS dose. Intraoperative radiotherapy (IORT) is a potential alternative, however standard dose recommendations are lacking. METHODS AND MATERIALS: Twenty consecutive brain metastases treated with post-operative SRS were retrospectively compared to IORT plans generated for 10-30 Gy in 1 fraction to 0-5 mm by estimating the applicator size and distance from critical organs using pre-operative and post-operative MRI. Additionally, 7 consecutive patients treated with IORT 30 Gy to surface were compared to retrospectively generated SRS plans using the post-operative MRI to 15-20 Gy and 30 Gy in 1 fraction marginal dose. RESULTS: For the 20 resection cavities treated with SRS and retrospectively compared to IORT, IORT from 10 to 30Gy resulted in lower or not significantly different doses to the optic apparatus and brainstem. Comparatively for the 7 patients treated with IORT 30 Gy to retrospective SRS plans to standard 15-20 Gy and 30 Gy marginal dose, IORT resulted in significantly lower doses to the optic apparatus and brainstem. At a median follow-up of 6.2 months, 86% of patients treated with surgery and IORT achieved local control and 0% developed radiographic or symptomatic radiation necrosis. CONCLUSIONS: Critical organ dosimetry for IORT remains generally lower than that achieved with single fraction SRS following resection of large brain metastases. We recommend 30 Gy to surface as the preferred prescription, consistent with the dose recommendation for IORT in glioblastoma used in the ongoing INTRAGO-II phase-III trial. Early clinical outcomes appear promising for surgery and IORT.

Delayed radiation-induced inflammation accompanying a marked carbohydrate antigen 19-9 elevation in a patient with resected pancreatic cancer.

Although carbohydrate antigen (CA) 19-9 is a useful tumor marker for pancreatic cancer, it can also become elevated from a variety of benign and malignant conditions. Herein we describe an unusual presentation of elevated CA 19-9 in an asymptomatic patient who had previously undergone adjuvant chemotherapy and radiation therapy for resected early stage pancreatic cancer. The rise in CA 19-9 might be due to delayed radiation-induced inflammation related to previous intra-abdominal radiation therapy with or without radiation recall induced by gemcitabine. After treatment with corticosteroids the CA 19-9 level decreased to normal, and the patient has not developed any evidence of recurrent cancer to date.

Using [(18)F]Fluorothymidine Imaged With Positron Emission Tomography to Quantify and Reduce Hematologic Toxicity Due to Chemoradiation Therapy for Pelvic Cancer Patients.

PURPOSE: The purpose of the present prospective clinical trial was to determine the efficacy of [(18)F]fluorothymidine (FLT)-identified active bone marrow sparing for pelvic cancer patients by correlating the FLT uptake change during and after chemoradiation therapy with hematologic toxicity. METHODS AND MATERIALS: Simulation FLT positron emission tomography (PET) images were used to spare pelvic bone marrow using intensity modulated radiation therapy (IMRT BMS) for 32 patients with pelvic cancer. FLT PET scans taken during chemoradiation therapy after 1 and 2 weeks and 30 days and 1 year after completion of chemoradiation therapy were used to evaluate the acute and chronic dose response of pelvic bone marrow. Complete blood counts were recorded at each imaging point to correlate the FLT uptake change with systemic hematologic toxicity. RESULTS: IMRT BMS plans significantly reduced the dose to the pelvic regions identified with FLT uptake compared with control IMRT plans (P<.001, paired t test). Radiation doses of 4 Gy caused an ∼50% decrease in FLT uptake in the pelvic bone marrow after either 1 or 2 weeks of chemoradiation therapy. Additionally, subjects with more FLT-identified bone marrow exposed to ≥4 Gy after 1 week developed grade 2 leukopenia sooner than subjects with less marrow exposed to ≥4 Gy (P<.05, Cox regression analysis). Apparent bone marrow recovery at 30 days after therapy was not maintained 1 year after chemotherapy. The FLT uptake in the pelvic bone marrow regions that received >35 Gy was 18.8% ± 1.8% greater at 30 days after therapy than at 1 year after therapy. The white blood cell, platelet, lymphocyte, and neutrophil counts at 1 year after therapy were all lower than the pretherapy levels (P<.05, paired t test). CONCLUSIONS: IMRT BMS plans reduced the dose to FLT-identified pelvic bone marrow for pelvic cancer patients. However, reducing hematologic toxicity is challenging owing to the acute radiation sensitivity (∼4 Gy) and chronic suppression of activity in bone marrow receiving radiation doses >35 Gy, as measured by the FLT uptake change correlated with the complete blood cell counts.

Risk of radiation-induced malignancy with heterotopic ossification prophylaxis: a case-control analysis.

PURPOSE: To determine the risk of radiation-induced malignancy after prophylactic treatment for heterotopic ossification (HO). METHODS AND MATERIALS: A matched case-control study was conducted within a population-based cohort of 3489 patients treated either for acetabular fractures with acetabular open reduction internal fixation or who underwent total hip arthroplasty from 1990 to 2009. Record-linkage techniques identified patients who were diagnosed with a malignancy from our state health registry. Patients with a prior history of malignancy were excluded from the cohort. For each documented case of cancer, 2 controls were selected by stratified random sampling from the cohort that did not develop a malignancy. Matching factors were sex, age at time of hip treatment, and duration of follow-up. RESULTS: A total of 243 patients were diagnosed with a malignancy after hip treatment. Five patients were excluded owing to inadequate follow-up time in the corresponding control cohort. A cohort of 238 cases (control, 476 patients) was included. Mean follow-up was 10 years, 12 years in the control group. In the cancer cohort, 4% of patients had radiation therapy (RT), compared with 7% in the control group. Of the 9 patients diagnosed with cancer after RT, none occurred within the field. The mean latency period was 5.9 years in the patients who received RT and 6.6 years in the patients who did not. Median (range) age at time of cancer diagnosis in patients who received RT was 62 (43-75) years, compared with 70 (32-92) years in the non-RT patients. An ad hoc analysis was subsequently performed in all 2749 patients who were not matched and found neither an increased incidence of malignancy nor a difference in distribution of type of malignancy. CONCLUSION: We were unable to demonstrate an increased risk of malignancy in patients who were treated with RT for HO prophylaxis compared with those who were not.

Where do patients with cancer in Iowa receive radiation therapy?

PURPOSE: Multiple studies have shown survival benefits in patients with cancer treated with radiation therapy, but access to treatment facilities has been found to limit its use. This study was undertaken to examine access issues in Iowa and determine a methodology for conducting a similar national analysis. PATIENTS AND METHODS: All Iowa residents who received radiation therapy regardless of where they were diagnosed or treated were identified through the Iowa Cancer Registry (ICR). Radiation oncologists were identified through the Iowa Physician Information System (IPIS). Radiation facilities were identified through IPIS and classified using the Commission on Cancer accreditation standard. RESULTS: Between 2004 and 2010, 113,885 invasive cancers in 106,603 patients, 28.5% of whom received radiation treatment, were entered in ICR. Mean and median travel times were 25.8 and 20.1 minutes, respectively, to the nearest facility but 42.4 and 29.1 minutes, respectively, to the patient's chosen treatment facility. Multivariable analysis predicting travel time showed significant relationships for disease site, age, residence location, and facility category. Residents of small and isolated rural towns traveled nearly 3× longer than urban residents to receive radiation therapy, as did patients using certain categories of facilities. CONCLUSION: Half of Iowa patients could reach their nearest facility in 20 minutes, but instead, they traveled 30 minutes on average to receive treatment. The findings identified certain groups of patients with cancer who chose more distant facilities. However, other groups of patients with cancer, namely those residing in rural areas, had less choice, and some had to travel considerably farther to radiation facilities than urban patients.

High resolution (3 Tesla) MRI-guided conformal brachytherapy for cervical cancer: consequences of different high-risk CTV sizes.

PURPOSE: To evaluate conventional brachytherapy (BT) plans using dose-volume parameters and high resolution (3 Tesla) MRI datasets, and to quantify dosimetric benefits and limitations when MRI-guided, conformal BT (MRIG-CBT) plans are generated. MATERIAL AND METHODS: Fifty-five clinical high-dose-rate BT plans from 14 cervical cancer patients were retrospectively studied. All conventional plans were created using MRI with titanium tandem-and-ovoid applicator (T&O) for delivery. For each conventional plan, a MRIG-CBT plan was retrospectively generated using hybrid inverse optimization. Three categories of high risk (HR)-CTV were considered based on volume: non-bulky (< 20 cc), low-bulky (> 20 cc and < 40 cc) and bulky (≥ 40 cc). Dose-volume metrics of D90 of HR-CTV and D2cc and D0.1cc of rectum, bladder, and sigmoid colon were analyzed. RESULTS: Tumor coverage (HR-CTV D90) of the conventional plans was considerably affected by the HR-CTV size. Sixteen percent of the plans covered HR-CTV D90 with the prescription dose within 5%. At least one OAR had D2cc values over the GEC-ESTRO recommended limits in 52.7% of the conventional plans. MRIG-CBT plans showed improved target coverage for HR-CTV D90 of 98 and 97% of the prescribed dose for non-bulky and low-bulky tumors, respectively. No MRIG-CBT plans surpassed the D2cc limits of any OAR. Only small improvements (D90 of 80%) were found for large targets (> 40 cc) when using T&O applicator approach. CONCLUSIONS: MRIG-CBT plans displayed considerable improvement for tumor coverage and OAR sparing over conventional treatment. When the HR-CTV volume exceeded 40 cc, its improvements were diminished when using a conventional intracavitary applicator.

The dosimetric impact of vaginal balloon-packing on intracavitary high-dose-rate brachytherapy for gynecological cancer.

PURPOSE: We perform a clinical retrospective study to determine whether a vaginal balloon-packing system provides a dosimetric reduction to organs at risk (OARs) versus traditional gauze packing for gynecological high-dose-rate brachytherapy (HDR-BT). We also test various balloon filling materials for optimizing imaging quality. MATERIAL AND METHODS: Filling materials for balloon-packing were evaluated based on imaging quality with X-ray, computerized tomography, and magnetic resonance imaging modalities. We then retrospectively reviewed 45 HDR-BT plans of 18 patients performed with gauze packing and 39 plans of 16 patients performed with balloon-packing. Twelve patients received both gauze and balloon-packing. HDR-BT was delivered with an iridium-192 afterloader and a Fletcher-Suit-Declos-style T&O applicator. At each fraction, 3D imaging was obtained. The D2cc values of OARs were calculated, as well as ICRU-defined point doses. RESULTS: In the 84 HDR fractions reviewed, vaginal balloon-packing provides statistically equivalent doses to rectum, bladder, and sigmoid compared to gauze packing. On average balloon-packing produced average reductions of 3.3% and 6.9% in the rectal and sigmoid D2cc doses and an increase of 3.2% to the bladder D2cc dose (normalized to prescription dose), although none of these values were statistically significant for the twelve patients who received both gauze and balloon-packing (32 and 40 total fractions, respectively). CONCLUSIONS: In the 84 HDR fractions analyzed, vaginal balloon-packing is as effective as gauze packing for dose sparing to the rectum, bladder, and sigmoid. A 1: 1 solution of saline and contrast for filling material enables easy contouring for image-guided HDR with minimal artefacts.

The dosimetric impact of heterogeneity corrections in high-dose-rate ¹9²Ir brachytherapy for cervical cancer: Investigation of both conventional Point-A and volume-optimized plans.

PURPOSE: To evaluate the dosimetric impact of heterogeneity corrections on both conventional and volume-optimized high-dose-rate (HDR) ¹9²Ir brachytherapy tandem-and-ovoid treatment plans. METHODS AND MATERIALS: Both conventional and volume-optimized treatment plans were retrospectively created using eight unique CT data sets. In the volume-optimized plans, the clinical target volume (CTV) and organs-at-risk (rectum, bladder, and sigmoid) were contoured on the CT data sets by a single physician. For each plan, dose calculations representing homogeneous water medium were performed using the Task Group (TG-43) formalism and dose calculations with heterogeneity corrections were performed using a commercially available treatment planning system. RESULTS: For the conventional plans, the change in dose between TG-43 and heterogeneity-corrected calculations was assessed for the following points: Point-A (left and right) and International Commission on Radiation Units and Measurements (ICRU) 38 defined rectum and bladder points. It was found that the dose to the ICRU bladder decreased the most (-2.2±0.9%), whereas ICRU rectum (-1.7±0.8%), Point-A right (-1.1±0.4%), and Point-A left (-1.0±0.3%) also showed decreases with heterogeneity-corrected calculations. For the volume-optimized plans, the change in dose between TG-43 and heterogeneity-corrected calculations was assessed for the following dose-volume histogram parameters: D(90) of the CTV and D(2cc) of the rectum, bladder, and sigmoid. It was found that D(90) of the CTV decreased by -1.9±0.7% and D(2cc) decreased by -2.6±1.4%, -1.0±0.4%, and -2.0±0.6% for the rectum, bladder and sigmoid, respectively, with heterogeneity-corrected calculations. CONCLUSIONS: Heterogeneity corrections on high-dose rate plans were found to have only a small dosimetric impact over TG-43-based dose calculations for both conventional Point-A and volume-optimized plans.

Target volume changes through high-dose-rate brachytherapy for cervical cancer when evaluated on high resolution (3.0 Tesla) magnetic resonance imaging.

PURPOSE: To evaluate tumor volume changes that occurred during courses of high-dose-rate brachytherapy (HDR) using high resolution (3.0 Tesla) magnetic resonance imaging (MRI), along with the regression after external beam radiation therapy (EBRT). METHODS AND MATERIALS: Fourteen patients with International Federation of Gynecology and Obstetrics stage IB1-IV cervical cancer were studied retrospectively. All patients underwent EBRT with concurrent chemotherapy followed by HDR brachytherapy. Gross tumor volume (GTV) and high-risk clinical target volume (HR-CTV) were contoured on a 3.0 Tesla MRI on the day of the HDR and on diagnostic MRI (1.5 Tesla) prior to EBRT. Two physicians independently contoured the GTV and HR-CTV on a total of 46 MRI data sets for the HDR plans. The percent volume changes of GTV and HR-CTV were quantified after EBRT and again after each HDR. The conformity indices (CIs) of the 2 contours were assessed. RESULTS: GTV and HR-CTV considerably regressed after the first ( --31.7% ± 19.3% and --26.4% ± 6.9%, respectively) and the second (--26.8% ± 14.3% and --23.8% ± 11.0%) fraction of HDR while relatively small regressions were observed after the third (--16.3% ± 14.2% and --10.6% ± 13.4%) and the fourth (--8.0% ± 3.4% and --9.0% ± 8.0%) fractions. The lymph node-positive on positron emission tomography (PET) and stage III or IV group showed, on average, more than 200% larger GTV and HR-CTV before EBRT than those of the other patients. The GTV and HR-CTV for the group were larger on average more than 150% after EBRT and before the first HDR fraction than the other group. Interobserver CI did not vary significantly (0.75 ± 0.11) for HR-CTV, although a smaller CI (0.56 ± 0.21) was found for GTV. CONCLUSIONS: Larger tumor regressions were observed after the first and second fractions of HDR than after all subsequent fractions. The PET-identified lymph node-positive patient group and stage III or higher tumors showed larger tumor volumes before and after EBRT than other cases.